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The rabbit ear hypertrophic scar (HS) model has been widely used to study the mechanisms that underlie the development of HS as well as the effectiveness of various treatments. Although the rabbit ear HS model is well characterized in terms of scar formation, the rate and level of angiogenesis has not been investigated in this model, and the cause\u2010effect relationship between angiogenesis and rabbit HSs has not been examined. In the current study, full\u2010thickness excisional wounds were created on the ventral side of New Zealand White rabbit ears to induce HS formation, and the dynamic pattern of angiogenesis and the expression of angiogenic regulatory factors were examined over time. Blood vessel density was found to peak at 2.7% on day 14 post\u2010wounding, decreasing to 1.7% by day 28. mRNA levels of the proangiogenic factor VEGF\u2010A peaked at day 14, while the expression of the antiangiogenic factors pigment epithelium\u2010derived factor (PEDF) and thrombospondin 1 (TSP1) peaked at day 28 post\u2010wounding. To examine whether inhibition of angiogenesis influences HS formation in this model, wounds were treated with exogenous soluble antiangiogenic agents including recombinant PEDF (rPEDF) and a functional PEDF peptide (PEDF\u2010335). rPEDF and PEDF\u2010335 were administered intradermally from day 4 post\u2010wounding every 3\u2009days until day 19. Intradermal injection of rPEDF or PEDF\u2010335 both led to decreased angiogenesis and decreased collagen deposition at the wound site. The results support the utility of antiangiogenic therapies, including rPEDF\/PEDF\u2010335, as a potential new strategy for the prevention or treatment of HSs.<\/jats:p>","DOI":"10.1111\/wrr.12828","type":"journal-article","created":{"date-parts":[[2020,6,25]],"date-time":"2020-06-25T23:10:44Z","timestamp":1593126644000},"page":"684-695","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Pigment epithelium\u2010derived factor attenuates angiogenesis and collagen deposition in hypertrophic scars"],"prefix":"10.1111","volume":"28","author":[{"given":"Da","family":"Ma","sequence":"first","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Stomatology, Stomatological Hospital Guanghua School of Stomatology, SunYat\u2010sen University  Guangzhou Guangdong 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